A Clinical Trial Assessing BT-001 Alone and in Combination With Pembrolizumab in Metastatic or Advanced Solid Tumors

NCT04725331 | Terminated Phase 1 DMC

• 4 other identifiers: BT-001.012020-000505-80MK3475-E37KEYNOTE-E37
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 5

Brief Summary

This is a Phase I/IIa, multicenter, open-label, consecutive cohorts, dose-escalation study of BT-001 with repeated IT administrations alone and in combination with IV infusions of pembrolizumab.

Conditions

Metastatic Cancer; Soft Tissue Sarcoma; Merkel Cell Carcinoma; Melanoma; Triple Negative Breast Cancer; Non Small Cell Lung Cancer

Keywords

Superficial tumors; Metastatic cancer; Intratumoral; Safety; Oncolytic virus; Vaccinia virus; Solid tumors; Melanoma; Merkel; Sarcoma; TNBC; NSCLC; Pembrolizumab; BT-001; TG6030; Phase 1

Outcome Measures

Primary Outcomes (4)

• Phase I: Safety and tolerability (Adverse Event reported per NCI-CTCAE v5.0)

  Incidence of Adverse Event reported per NCI-CTCAE v5.0, Dose limiting toxicity and Serious Adverse Events.

  Up to 5 years

• Phase I, Part A: Recommended dose for Part B (RDPB) definition

  RDPB based on the safety data collected during the dose escalation phase (Phase I, Part A).

  Week 10-12

• Phase IIa (except Soft Tissue Sarcoma cohort): Immune Overall Response Rate (iORR) by iRECIST

  Percentage of patients whose best overall response is either a Complete Response or a Partial Response according to immune Response Evaluation Criteria In Solid Tumors (iRECIST) criteria over the the total number of evaluable patients. for injected and non-injected lesion(s)

  Up to 2 years

• Phase IIa (Soft Tissue Sarcoma cohort): Immune Disease Control Rate (iDCR) at 6 months by iRECIST

  Percentage of patients whose best overall response is either a Complete Response, a Partial Response or Stable Disease according to immune Response Evaluation Criteria In Solid Tumors (iRECIST) criteria over the the total number of evaluable patients.

  Up to 6 months

Secondary Outcomes (5)

• Phase IIa: Safety and tolerability (Adverse Event reported per NCI-CTCAE v5.0)

  Up to 5 years

• Disease Control Rate (DCR) and immune DCR by RECIST version 1.1 and iRECIST

  4 months or 6 months

• Progression Free Survival (PFS) and immune PFS duration by RECIST version 1.1 and iRECIST

  Up to 2 years

• Duration of overall Response (DoR) and immune DOR by RECIST version 1.1 and iRECIST

  Up to 2 years

• Overall Survival (OS) duration

  Up to 2 years

Study Arms (3)

Phase I, Part A - Dose escalation and safety of BT-001 alone

EXPERIMENTAL

Dose escalation with repeated administrations of BT-001 directly into tumor as a single agent, in patients with metastatic or advanced solid tumors.

Biological: BT-001

Phase I, Part B - Safety of BT-001 in combination with pembrolizumab

EXPERIMENTAL

Repeated administrations of BT-001 directly into tumor in combination with infusions of pembrolizumab in patients with metastatic or advanced soft tissue sarcoma (STS), Merkel cell carcinoma (MCC), melanoma, triple negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC)..

Biological: BT-001; Drug: Pembrolizumab [KEYTRUDA®]

Phase IIa - Expansion cohorts of BT-001 in combination with pembrolizumab

EXPERIMENTAL

Repeated administrations of BT-001 directly into tumor in combination with infusions of pembrolizumab in several cohorts of patients with defined metastatic or advanced solid tumor conditions: soft tissue sarcoma, Merkel cell carcinoma, melanoma, triple negative breast cancer, non-small cell lung cancer.

Biological: BT-001; Drug: Pembrolizumab [KEYTRUDA®]

Interventions

BT-001 BIOLOGICAL

Oncolytic Vaccinia virus containing genes encoding the 4-E03 human recombinant anti-hCTLA4 antibody and human GM-CSF administered at different dose \[Phase I, Part A\]; one dose lower and at Recommended Dose for Part B \[Phase I, Part B\] by intra-tumoral (IT) route.

Phase I, Part A - Dose escalation and safety of BT-001 alone; Phase I, Part B - Safety of BT-001 in combination with pembrolizumab; Phase IIa - Expansion cohorts of BT-001 in combination with pembrolizumab

Pembrolizumab [KEYTRUDA®] DRUG

Programmed death receptor (PD-1) blocking antibody administered at 200mg by intravenous (IV) infusions every 3 weeks.

Also known as: KEYTRUDA®

Phase I, Part B - Safety of BT-001 in combination with pembrolizumab; Phase IIa - Expansion cohorts of BT-001 in combination with pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have at least 1 injectable measurable cutaneous, subcutaneous or nodal lesion (direct injection or through the use of ultrasound guidance) not exceeding 50mm in longest diameter and whenever possible 1 distant non-injected measurable lesion.
• Provision of a fresh tumor sample of the lesion that will be injected first and, whenever possible, from another lesion that is planned to be injected, at baseline and be willing to supply new tumor samples from a biopsy during treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Have adequate hematological, hepatic and renal functions.
• Have histologically confirmed, advanced/metastatic sarcoma (soft tissue and bone), Merkel cell carcinoma, melanoma, triple negative breast cancer or non-small cell lung cancer, with cutaneous or, palpable subcutaneous lesions or easily injectable lymph nodes.
• Have failed and/or are intolerant to standard therapeutic options.

You may not qualify if:

• Have had major surgery within 4 weeks of first study drug administration.
• Have received prior treatment with a vaccinia oncolytic virus.
• Have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the start of treatment.
• Have received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 28 days prior the first dose of study drugs
• Have a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Have a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
• Have an active infection requiring systemic therapy
• Have a known history of HIV infection
• Is taking an anticoagulant medication that cannot be interrupted prior to IT injections
• Have had an allogenic tissue/solid organ transplant or allogenic stem cell or bone marrow transplantation
• History of severe exfoliative skin conditions (e.g., eczema or atopic dermatitis) requiring systemic therapy for more than 4 weeks within 2 years prior to BT-001 initiation.
• Have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immune-related Adverse Event (irAE).
• Have known active CNS metastases and/or carcinomatous meningitis.

Sponsors & Collaborators

• Transgene: lead
• BioInvent International AB: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

Clinique Universitaire Saint-Luc

Brussels, 1200, Belgium

Location

Institut Bergonié

Bordeaux, 33000, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hôpital Saint-Louis AP-HP

Paris, 75010, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Sarcoma; Carcinoma, Merkel Cell; Melanoma; Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Vaccinia

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Poxviridae Infections

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: January 26, 2021
• Study Start: February 25, 2021
• Primary Completion: October 22, 2025
• Study Completion: October 22, 2025
• Last Updated: November 21, 2025

Record last verified: 2025-11

Locations

FR (4); BE (1)